Intravenous (IV) drug users remain the second largest group of persons who have developed the acquired immunodeficiency syndrome (AIDS). IV drug users are also the primary link to two other case groups for AIDS--heterosexual partners and children. The proposed study is a continuation and expansion of a prospective research design in which IV drug users are studied over time to determine behavioral risk factors for exposure to HTLV-III/LAV; the development of different manifestations of HTLV-III/LAV infection, from "normal" immune functioning through surveillance definition AIDS; and cofactors that may influence the infection process. Potential cofactors to be investigated include continued drug injection, needle sharing and cleaning behaviors, specific drugs used, sexual behavior, and exposure to various other bacterial and virologic agents. The study also includes investigation of possible increased susceptibility to specific infections--tuberculosis, pneumonia, and endocarditis--that have been ecologically associated with HTLV-III/LAV among drug users. The subjects will be 600 IV drug users located through drug treatment programs; 400 of them are being studied and 200 will be added. The additional subjects will allow more successful study of the development of surveillance definition AIDS and examination of the possible effectiveness of current risk reduction efforts among IV drug users. The new cohort will oversample female IV drug users to permit closer study of the sex differences found in our current research, which include differences in rates of Kaposi's sarcoma, HTLV-III/LAV antibody prevalence and risk reduction behavior. Data will be collected from all subjects every 8 months. They will be interviewed about medical history, drug use, and other potential cofactors, have blood samples taken, and undergo brief physical examinations for oral thrush and lymphadenopathy. Blood analyses will include lymphocyte subsets and HTLV-III/LAV antibody. The proposed research includes ethnographic study of responses to the AIDS epidemic among IV drug users. Special substudies will focus on maintenance of currently observed risk reduction, new recruitment into IV drug use, and efforts to avoid heterosexual and in utero transmission of HTLV-III/LAV.